title: MCP-1 -2518 A/G functional polymorphism is associated with increased susceptibility to active pulmonary tuberculosis in Tunisian patients.
abstract: Monocyte chemoattractant protein-1 (MCP-1) plays crucial role in protective immunity against Mycobacterium tuberculosis (MT). In this study, we examined whether single nucleotide polymorphism (SNP) -2518 A/G (rs 1024611) of MCP-1 affect the susceptibility to active tuberculosis (TB) in Tunisian populations. Genomic DNA from patients with active TB (168 cases of pulmonary TB and 55 cases of extrapulmonary TB) and ethnically controls (150 cases) was genotyped for the MCP-1 -2518 A/G SNP by polymerase chain reaction fragment length polymorphism (PCR-RFLP). We observed that -2518 G allele and GG genotype (high MCP-1 producer) frequencies were significantly more elevated in active pulmonary TB group in comparison to control group [34 vs. 22%; P = 0.0007; 15 vs. 5%, P corrected for the number of genotypes (Pc) = 0.015; respectively]. Additionally, they were associated with increased risk development of this clinical form of TB [odds ratio (OR) = 1.83, 95% confidence intervals (CI) = 1.26-2.66; OR = 3.1, 95% CI = 1.28-7.76; respectively]. However, wild type allele -2518 A and AA genotype were over-represented in control group (78 and 62%) and seem to be protective factors against TB. Moreover, -2518 AA genotype was more frequent in control group and was associated with resistance against development of active pulmonary TB (OR = 0.56, 95% CI = 0.35-0.89, Pc = 0.03). Our findings confirm the key role of -2518 A/G SNP of MCP-1 and support its association with resistance/susceptibility to the development of active pulmonary TB in the Tunisian population.
authors.affiliation: Laboratory of Microbiology and Immunology, UR02SP13, Farhat Hached University Hospital, CHU Farhat Hached - Av. Ibn el Jazzar, 4000 Sousse, Tunisia. wbenselma@hotmail.com
authors.forename: Walid
authors.initials: W
authors.lastname: Ben-Selma
authors.forename: Hedi
authors.initials: H
authors.lastname: Harizi
authors.forename: Jalel
authors.initials: J
authors.lastname: Boukadida
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000235:genetics*; D003710:Demography; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014397:Tuberculosis, Pulmonary / Q000235:genetics*; D014416:Tunisia; D055815:Young Adult
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2